Anti-Osteoclast Therapy as Neoadjuvant in Treatment of Chondrosarcoma - Phase 1b Trial
- Registration Number
- NCT03173976
- Lead Sponsor
- Mohammed Milhem
- Brief Summary
The purpose of this single arm open label phase 1b clinical study is to see what effect zoledronic acid has on tumors in patients with resectable any grade chondrosarcoma prior to surgery.
- Detailed Description
This is a single arm open label phase 1b clinical trial assessing the safety and efficacy of neoadjuvant zoledronic acid in patients with resectable any grade chondrosarcoma as measured by pathological characteristics and recurrence free survival. Prior to surgery, subjects will receive 1 standard dose of IV zoledronic acid given over 15 minutes. Surgery will be performed 21-31 days after the dose as per standard of care. The second standard dose of zoledronic acid will be given 3 weeks after surgery.
Phase 1b:
The Phase 1b portion of this study is to ensure the safety and tolerability of standard dose of zoledronic acid intravenously as assessed by incidence of dose limiting toxicities (DLT). Although the safety of use of this drug has been established in patients with bone metastases from solid tumors (breast, prostate) and in patients with hypercalcemia of malignancy and multiple myeloma, it has not been tested in patients with chondrosarcoma. Surgery will be performed between day 21 to 31 from the dose of zoledronic acid to allow its effect on the tumor and resolution of toxicities. A total of 6 patients will be enrolled in this run-in phase 1b. Patients will be followed post operatively as per NCCN guidelines (for years 1 and 2) with local and systemic imaging.
Expansion Cohort:
The phase 1 b expansion cohort of the study will provide an estimate of the relative treatment effect of zoledronic acid on any grade chondrosarcoma specimens. Subjects will receive a total of 2 doses of zoledronic acid, one dose prior to surgery and the second dose 21 days after surgery. Patients will undergo standard of care surgery 21-31 days from the first dose of zoledronic acid. 9 subjects will be enrolled in this cohort for a total of 15 planned subject enrollment over 3 years. Patients will be followed post operatively for recurrence with imaging and survival and as per NCCN guidelines (for years 1 and 2).
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 17
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Zoledronic Acid Zoledronic Acid 1 cycle of Zoledronic Acid (ZA) at 4mg IVP prior to surgery and a second cycle of ZA at 4 mg IVP 3 weeks after surgery
- Primary Outcome Measures
Name Time Method Phase 1b cohort: Dose Limiting Toxicity - to examine the toxicity related to the therapy by measuring the number of treatment related adverse events in patients All eligible patients that have initiated treatment will be considered evaluable for assessing adverse event rate(s) up to 4 weeks post Cycle 2 Toxicity will be assessed using the NIH-NCI Common Terminology Criteria for Adverse Events, version 4.0 (CTCAEv4.)
Expansion cohort: Response Rate - Change at evaluations Changes on 2 consecutive evaluations at screening phase (days 1-14); Cycle 2 at 3 weeks post operatively; EOT visit at 4 weeks post Cycle 2; and then at follow up visits every 6 months for up to 5 years. Response and progression will be assessed by tumor viability, osteoclast activity, and bone destruction compared to the initial biopsy in subjects with localized any grade chondrosarcoma.
- Secondary Outcome Measures
Name Time Method Recurrence (local or metastatic) free survival All eligible patients that have initiated treatment will be considered evaluable for assessing recurrence free survival for up to 2 years. Recurrence-free survival will be estimated using the Kaplan-Meier method.
Overall survival All eligible patients that have initiated treatment will be considered evaluable for assessing overall survival up to 5 years. Overall survival will be estimated using the Kaplan-Meier method.
Trial Locations
- Locations (1)
University of Iowa Hospitals and Clinics
🇺🇸Iowa City, Iowa, United States